Delivering Tumor Treating Fields (TTFields) Using Implantable Transducer Arrays

ABSTRACT

Tumor treating fields (TTFields) can be delivered by implanting a plurality of sets of implantable electrode elements within a person&#39;s body. Temperature sensors positioned to measure the temperature at the electrode elements are also implanted, along with a circuit that collects temperature measurements from the temperature sensors. In some embodiments, an AC voltage generator configured to apply an AC voltage across the plurality of sets of electrode elements is also implanted within the person&#39;s body.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. Ser. No. 18/109,539, filedFeb. 14, 2023, which is a divisional of U.S. Ser. No. 17/942,910, filedSep. 12, 2022, now U.S. Pat. No. 11,607,543, issued Mar. 21, 2023, whichis a continuation of U.S. Ser. No. 16/801,972, filed Feb. 26, 2020, nowU.S. Pat. No. 11,471,676, issued Oct. 18, 2022, which claims the benefitof U.S. Provisional Application 62/811,311, filed Feb. 27, 2019, each ofwhich is incorporated herein by reference in its entirety.

BACKGROUND

TTFields (Tumor Treating Fields) therapy is a proven approach fortreating tumors. Referring to FIG. 1 , in the prior art Optune® systemfor delivering TTFields, the TTFields are delivered to patients via fourtransducer arrays placed on the patient's skin in close proximity to atumor. The transducer arrays are arranged in two pairs. One of thosepairs (A/A) is positioned on the left and right sides of the head; andthe other one of those pairs (B/B) is positioned on the front and backof the head. Each transducer array is connected via a multi-wire cableto an AC voltage generator. The AC voltage generator (a) sends an ACcurrent through one pair of arrays during a first period of time; then(b) sends an AC current through the other pair of arrays during a secondperiod of time; then repeats steps (a) and (b) for the duration of thetreatment.

Each transducer array is configured as a set of capacitively coupledelectrode elements (about 2 cm in diameter) that are interconnected viaflex wires. Each electrode element includes a ceramic disk that issandwiched between a layer of an electrically conductive medical gel andan adhesive tape. When placing the arrays on the patient, the medicalgel adheres to the contours of the patient's skin and ensures goodelectric contact of the device with the body. The adhesive tape holdsthe entire array in place on the patient as the patient goes about theirdaily activities.

The amplitude of the alternating current that is delivered via thetransducer arrays is controlled so that skin temperature (as measured onthe skin below the transducer arrays) does not exceed a safety thresholdof 41° C. The temperature measurements on the patient's skin areobtained using thermistors placed beneath some of the disks of thetransducer arrays. In the existing Optune® system, each array includes 8thermistors, with one thermistor positioned beneath a respective disk inthe array. (Note that most arrays include more than 8 disks, in whichcase the temperature measurements are only performed beneath a sub-setof the disks within the array).

The thermistors in each of the four arrays are connected via long wiresto an electronic device called the “cable box” where the temperaturefrom all 32 thermistors (4 arrays×8 thermistors per array A, A, B, B) ismeasured and analog-to-digital converted into digital values for eachthermistor. These measurements are then transmitted from the cable boxto the AC voltage generator via an additional two wires that facilitatetwo-way digital serial communications between the cable box and the ACvoltage generator. The controller in the AC voltage generator uses thetemperature measurements to control the current to be delivered via eachpair of arrays A, A, B, B in order to maintain temperatures below 41° C.on the patient's skin. The current itself is delivered to each array viaan additional wire (i.e., one wire for each array) that runs from the ACvoltage generator through the cable box to the array.

In the existing Optune® system there are four long 10-wire cables (eachof which runs between a respective array and the cable box) and one8-wire spiral cord that runs between the AC voltage generator and thecable box. Each of the 10-wire cables has 8 wires for carrying signalsfrom the 8 thermistors, 1 wire for the common of all 8 thermistors, plus1 wire for providing the TTFields signal to the array. The 8-wire spiralcord has 1 wire for power to the cable box (Vcc), 1 wire for ground tothe cable box, 2 wires for data communication (to send the temperaturereadings to the AC voltage generator), plus 4 wires for the TTFieldssignals (i.e., one for each of the four arrays).

SUMMARY OF THE INVENTION

One aspect of the invention is directed to a first apparatus fordelivering tumor treating fields. The first apparatus comprises aplurality of sets of electrode elements, and each of the sets ofelectrode elements is configured for implantation within a person'sbody. The first apparatus also comprises a plurality of temperaturesensors configured for implantation within the person's body andpositioned with respect to the sets of electrode elements to measure atemperature at each of the sets of electrode elements. The firstapparatus also comprises a circuit configured for implantation withinthe person's body configured for collecting temperature measurementsfrom the plurality of temperature sensors. And the first apparatus alsocomprises an AC voltage generator configured for implantation within theperson's body and configured to apply an AC voltage across the pluralityof sets of electrode elements.

Some embodiments of the first apparatus further comprise an inductivelycoupled circuit configured for implantation within the person's body andconfigured to power the AC voltage generator.

Some embodiments of the first apparatus further comprise a batteryconfigured for implantation within the person's body and configured topower the AC voltage generator. Optionally, these embodiments mayfurther comprise an inductively coupled circuit configured forimplantation within the person's body and configured to charge thebattery.

In some embodiments of the first apparatus, each of the sets ofelectrode elements comprises a plurality of capacitively coupledelectrode elements. Optionally, in these embodiments, each of thecapacitively coupled electrode elements comprises a ceramic disc.

In some embodiments of the first apparatus, each of the temperaturesensors comprises a thermistor. In some embodiments of the firstapparatus, the plurality of sets of electrode elements, the plurality oftemperature sensors, the circuit, and the AC voltage generator are allimplanted in the person's body.

Another aspect of the invention is directed to a second apparatus fordelivering tumor treating fields. The second apparatus comprises aplurality of sets of electrode elements, and each of the sets ofelectrode elements is configured for implantation within a person'sbody. The second apparatus also comprises a plurality of temperaturesensors configured for implantation within the person's body andpositioned to measure a temperature at each of the sets of electrodeelements. And the second apparatus also comprises a circuit configuredfor implantation within the person's body configured for collectingtemperature measurements from the plurality of temperature sensors.

In some embodiments of the second apparatus, each of the sets ofelectrode elements comprises a plurality of capacitively coupledelectrode elements. In some embodiments of the second apparatus, each ofthe temperature sensors comprises a thermistor. In some embodiments ofthe second apparatus, the plurality of sets of electrode elements, theplurality of temperature sensors, and the circuit are all implanted inthe person's body.

Another aspect of the invention is directed to a third apparatus fordelivering tumor treating fields. The third apparatus comprises aplurality of sets of electrode elements, and each of the sets ofelectrode elements is configured for implantation within a person'sbody. The third apparatus also comprises a plurality of temperaturesensors configured for implantation within the person's body andpositioned to measure a temperature at each of the sets of electrodeelements, And the third apparatus also comprises an AC voltage generatorconfigured for implantation within the person's body and configured toapply an AC voltage across the plurality of sets of electrode elements.

Some embodiments of the third apparatus further comprise an inductivelycoupled circuit configured for implantation within the person's body andconfigured to power the AC voltage generator.

Some embodiments of the third apparatus further comprise a batteryconfigured for implantation within the person's body and configured topower the AC voltage generator. Optionally, these embodiments mayfurther comprise an inductively coupled circuit configured forimplantation within the person's body and configured to charge thebattery.

In some embodiments of the third apparatus, each of the sets ofelectrode elements comprises a plurality of capacitively coupledelectrode elements. Optionally, in these embodiments, each of thecapacitively coupled electrode elements may comprise a ceramic disc.

In some embodiments of the third apparatus, each of the temperaturesensors comprises a thermistor. In some embodiments of the thirdapparatus, the plurality of sets of electrode elements, the plurality oftemperature sensors, and the AC voltage generator are all implanted inthe person's body.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram of the prior art Optune® system that is usedfor delivering TTFields to a person's head.

FIG. 2 is a block diagram of an embodiment that reduces the number ofconductors in each cable that must pass through the patient's skin.

FIG. 3 is a block diagram of an embodiment in which both the transducerarrays and the hub are implanted in the patient's body.

FIG. 4 depicts another approach that uses implantable electrodes inwhich the electrodes, the hub, and the AC voltage generator are allimplanted within the patient's body.

FIG. 5 depicts a variation on the FIG. 4 embodiment in which power isprovided to the hub and the AC voltage generator using a wirelessconnection.

FIG. 6 depicts an embodiment that uses implanted electrodes that ispowered by an implanted battery.

FIG. 7 depicts an embodiment that can switch the current to eachindividual electrode element on or off based on the state of a set ofelectrically controlled switches.

FIG. 8 is a schematic diagram of a circuit that is suitable forimplementing the switches in the FIG. 7 embodiment.

Various embodiments are described in detail below with reference to theaccompanying drawings, wherein like reference numerals represent likeelements, and wherein dotted lines represent implanted components.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Instead of using transducer arrays positioned on the patient's skin todeliver TTFields (as in the FIG. 1 embodiment described above), theembodiments described herein use transducer arrays that are implantedwithin a patient's body to deliver TTFields Implanting the transducerarrays can provide a number of potential advantages. These potentialadvantages include (1) hiding of the arrays from people with whom thepatient interacts; (2) improving patient comfort (by avoiding the skinirritation, sensations of heating, and/or limitations on motion that canresult from arrays that are positioned on the patient's skin); (3)improving electrical contact between the transducer arrays and thepatient's body; (4) eliminating the need for shaving regions on whichthe arrays are placed (as hair growth can interfere with the delivery ofTTFields); (5) avoiding the risk that detachment of the transducerarrays will interrupt the delivery of TTFields; (6) significantlyreducing the power required to deliver TTFields (e.g., by reducing thephysical distance between the transducer arrays and the tumor andbypassing anatomical structures that have high resistivity, e.g., theskull); (7) significantly reducing the weight of the device that must becarried by the patient (e.g., by using smaller batteries to takeadvantage of the reduced power requirements); (8) avoiding the skinirritation that can occur when transducer arrays are positioned on thepatient's skin; and (9) making it possible to deliver TTFields toanatomic structures that cannot be treated using transducer arrayspositioned on the patient's skin (e.g., the spinal cord, which issurrounded by highly conductive cerebrospinal fluid that is in turnsurrounded by the bony structure of the spine, both of which interferewith the penetration of TTFields into the spinal cord itself).

Note that in all of the embodiments described herein, it is important toinclude sensors for measuring temperature (such as thermistors) on ornear the transducer arrays so that tissue temperature can be controlledand thermal damage to tissue avoided. In situations where a giventransducer array is made up of a plurality of individual elements (e.g.,ceramic discs) it is preferable to distribute a plurality of temperaturesensors (e.g., thermistors) among the plurality of individual elements.

One approach (not shown) for using implantable electrodes has a blockdiagram that is similar to the prior art FIG. 1 embodiment describedabove, except that the transducer arrays A, A, B, B are all implanted inthe patient's body (e.g., between the scalp and the skull, or adjacentto the dura). While this approach enjoys advantages 1-8 listed above, italso suffers from a number of disadvantages. More specifically, each ofthe transducer arrays is connected to the cable box/AC voltage generatorvia a relatively long and bulky 10-conductor cable that extends outsideof the body through a surgical incision or port (1 conductor forapplying the AC voltage to the respective transducer array, plus 9conductors that are used to obtain temperature readings from 8 differentlocations on the respective transducer array). The use of 10 conductorcables could make the system cumbersome. In addition, including acomponent that passes through the person's skin into the person's headraises the risk of acquiring an infection, which can be particularlyproblematic in the context of the brain.

FIG. 2 depicts an improvement with respect to the approach described inthe previous paragraph. In this approach, the number of conductors ineach cable that must pass through the patient's skin is reduced from 10to 4, which will significantly reduce the bulk and size of those cables.This may be accomplished, for example, by implanting additionalelectronics E adjacent to each of the implanted transducer arrays A, Band using a hub-based architecture. When the hub-based architecture isused, each of the electronic blocks E includes a multiplexor thatreduces the number of conductors required for obtaining temperaturemeasurements from 9 to 3, and a hub 30 h is used to collect thetemperature readings from each of the transducer arrays and forwardthose readings to the AC voltage generator 30 g. The AC voltagegenerator 30 g can then control the current that is applied to each ofthe transducer array pairs A/A, B/B in order to ensure that thetransducer arrays do not overheat. Examples of circuitry that may beused to implement these electronic blocks E and the hub can be found inUS 2018/0050200, entitled Temperature Measurement in Arrays forDelivering TTFields, which is incorporated herein by reference in itsentirety. Note that while this embodiment does reduce the size and bulkof the wires that must pass through the person's skin, and providesadvantages 1-8 listed above, it does not alleviate the risk of infectionthat is associated with a component that passes through the person'sskin into the person's head.

FIG. 3 depicts a variation on the FIG. 2 approach. In the FIG. 3embodiment, instead of positioning the hub outside the patient's bodyand running four cables through the patient's skin (as in FIG. 2 ), theelectronics E, the transducer arrays A, B, and the hub 30 h areimplanted in the patient's body. In this FIG. 3 embodiment, only asingle cable (i.e., the cable that runs between the hub 30 h and the ACvoltage generator 30 g) must pass through the patient's skin.Optionally, this cable is connectorized using the depicted port 12. Inthe example depicted in FIG. 3 , the hub 30 h is positioned somewhere inthe patient's thorax, and four 4-conductor cables run between theelectronics E and the transducer arrays A, B in the patient's head andthe hub 30 h in the patient's thorax. This positioning is advantageousbecause there are no wires that pass directly from the outside worlddirectly into the patient's head, thereby reducing the risk of a seriousinfection. But in variations of the FIG. 3 embodiment, the hub 30 h maybe positioned in the patient's head, in which case the port 12 thatprovides access would also be positioned in the patient's head.

In these FIG. 3 embodiments, the hub 30 h collects temperaturemeasurements from each of the transducer arrays A, B via the electronicsE and forwards those temperature measurements to the AC voltagegenerator 30 g via the port 12. The AC voltage generator 30 g can thencontrol the current that is applied to each of the transducer arraypairs A/A, B/B in order to ensure that the transducer arrays do notoverheat. This embodiment also provides advantages 1-8 listed above.

FIG. 4 depicts another approach that uses implantable electrodes andalso provides advantages 1-8 listed above. In this embodiment, theelectrodes A, B, the hub 30 h, and the AC voltage generator 30 g are allimplanted within the patient's body. Power for the hub 30 h and the ACvoltage generator 30 g is provided via a port 14 that is positionedsomewhere on the patient's skin (e.g. in the thorax). The power source(e.g. the battery) in this embodiment is external, and the batteryprovides power to the hub 30 h and AC voltage generator 30 g via theport. The port 14 is connected to the hub 30 h and AC voltage generator30 g via appropriate wiring (e.g. a two conductor cable).

Since effective delivery of TTFields requires delivery of power on theorder of 10-100 W, care must be taken to minimize heat dissipation inall embodiments where the AC voltage generator 30 g is implanted withina patient's body (including this FIG. 4 embodiment). This is because anyinefficiencies will lead to heating of tissue surrounding the fieldgenerator, which could lead to thermal damage of tissue in the patient'sbody. To accomplish this, the AC voltage generator 30 g must operatewith very high efficiency. One example of a circuit that is suitable forimplementing a high efficiency AC voltage generator is described in U.S.Pat. No. 9,910,453, entitled High Voltage, High Efficiency Sine WaveGenerator with Pre-Set Frequency and Adjustable Amplitude, which isincorporated herein by reference in its entirety.

The AC voltage generator 30 g in these embodiments may optionallyoperate by starting with a low-voltage AC signal and amplifying andfiltering that signal using circuitry integrating a transformer and LCfilter. In some embodiments, an independent circuit combining thetransformer and LC filter could be connected to each transducer array(or even to each element of each transducer array). In theseembodiments, the low-voltage signal generator could be connected to eacharray (or element) via a wire placed remotely from the arrays. In thisconfiguration, heat generated through losses within the system would bespread over a larger volume thereby reducing the risk of thermal damageto tissue, while enabling delivery of higher field intensities. Tofurther reduce losses, the circuit on each array (or element) could bedesigned with a switch that switches the low voltage signal coming fromthe signal generator, thereby potentially reducing the losses within thesystem associated with switching at the arrays.

Optionally, the power source in the FIG. 4 embodiment may comprisemultiple small batteries that are woven into a piece of clothing. Thistype of design would enable delivery of high power for extended periodsof time while minimizing patient discomfort.

FIG. 5 depicts a variation on the FIG. 4 embodiments that also providesadvantages 1-8 listed above. In the FIG. 5 embodiments, instead ofproviding power to the hub 30 h and AC voltage generator 30 g directlyvia a wired connection that passes from the outside world into thepatient's body via a port 14 that is installed on the person's skin (asin FIG. 4 ), power in the FIG. 5 embodiment is provided to the hub 30 hand the AC voltage generator 30 g using a wireless connection. This maybe accomplished, for example, by implanting a first circuit 21 insidethe patient's body close to the patient's skin. The first circuit isconfigured to receive energy via inductive coupling. A second circuit 22(which may optionally be powered by a battery and/or the AC main) isconfigured to transmit energy to the first circuit 21 via inductivecoupling. The second circuit 22 is positioned outside the patient's bodyadjacent to the first circuit 21 during operation, so that energy can beinductively coupled from the second circuit 22 into the first circuit21. The construction of these circuits 21, 22 for transmitting andreceiving energy via inductive coupling are well known in the art andare commonly used, for example, for charging cell phones etc.

Optionally, the bulk and weight of the hardware that must be carriedaround by the patient can be advantageously reduced by providingmultiple copies of the second circuit 22 at various locations that arefrequented by the patient. For example, one copy of the second circuit22 may be provided at the patient's office, a second copy of the secondcircuit 22 may be provided in the patient's car, a third copy of thesecond circuit 22 may be provided in the patient's living room, and afourth copy of the second circuit 22 may be provided in or near thepatient's bed. When multiple copies of the second circuit 22 areprovided, the patient places the inductive coupling region of whicheversecond circuit 22 is nearby adjacent to the first circuit 21 implantedin their body so that the nearby second circuit 22 can power theimplanted AC voltage generator 30 g via inductive coupling. Thisarrangement can be particularly advantageous for people that movebetween various locations in a repeatable pattern (e.g., people whodrive to work in the same car every day, work at the same desk everyday, relax in the same living room every evening, and sleep in the samebed every night. Optionally, multiple copies of the second circuit 22may be incorporated into a mattress so that the patient will not have tobe hooked up to wires when they sleep, and can move around on themattress.

FIG. 6 depicts yet another embodiment that uses implanted electrodes andalso provides advantages 1-8 listed above. Notably, the battery 25 inthe FIG. 6 embodiment is implanted in the patient's body, and theimplanted battery 25 is charged via induction. One challenge with thisdesign is that the implanted battery 25 has to store relatively largeamounts of energy. Thus, charging the battery 25 via induction mayrequire the creation of large magnetic fluxes over extended periods oftimes. One method for overcoming this problem is a system in which amattress incorporating a coil is used. The patient sleeps on thismattress, and the battery powering the TTFields device is charged as thepatient sleeps. In other embodiments, the coil could surround the bed.

Alternatively, a transcutaneous energy transfer system (see, e.g.,Dissanayake et. al., IFMBE proceeding vol. 23) could be used to chargethe implanted battery 25. In this case, a coil connected to a circuitdesigned to charge the implanted battery would be implantedtranscutaneously. Charging would be performed with a separate device 24,which the patient would place close to the implanted coil 23. Theexternal device could be fixed to the patient's body using a garmentdesigned to fit tightly to the body, or using a medical adhesive. Thepatient would only be required to use the external charger when chargingthe implanted battery. This could occur for instance at night, while thepatient is sleeping, thereby minimizing the need for the patient tocarry an external device.

Optionally, the implanted transducer array elements may be configured topermit dynamic alteration of the field distribution in order to optimizedelivery of TTFields. Unlike the situation with external transducerarrays, once the transducer arrays have been implanted it will beimpractical to adjust the position of the transducer arrays in order tooptimize the field distribution within the patient's body. A differentapproach for controlling the field distribution within the patient'sbody is therefore desirable when implantable arrays are used. Onesuitable approach for this purpose would be to implant transducer arrayswith a relatively large number of switchable elements. The field canthen be shaped by choosing subsets of array elements that are switchedon when the field is delivered. As the tumor changes over time (responseor progression), the field distribution could be changed by changing thearray elements through which the field is generated.

Optionally, in any of the embodiments described above, the transducerarrays may be positioned on the dura. The advantage of thisconfiguration is that power required to deliver TTFields to the brainwould be reduced, because the field would not have to pass through thehighly resistive layer of the skull. At the same time, this placementwould reduce the need for invasive placement of the arrays in thebrain-reducing the risk of damage to brain tissue and possibly the riskof infections. This configuration would also enable delivery of TTFieldsto large portions of the brain, as opposed to only delivering theTTFields to the tumor. In some cases, treating large portions of thebrain may be advantageous. For instance, when treating the brain formetastases. In some embodiments, when treating regions of the body otherthan the head, the arrays could be placed subcutaneously to enabletreatment of large regions. In other embodiments, the arrays could beplaced in close proximity to the tumor. Placement in close proximity tothe tumor would enable localized delivery of TTFields and reduce thepower needed to deliver the fields.

In all of the embodiments described above, any component that isdescribed as being implanted must be configured for implantation beforeit is actually implanted in a person's body. This means that it must bedimensioned to fit within the location where it will be implanted, andthat all surfaces that might come into contact with tissue in theperson's body must be biocompatible.

Optionally, in any of the embodiments described above, when thetransducer arrays are implanted in the immediate vicinity of a tumor,the arrays could be made from or coated with a cytotoxic agent (e.g.,platinum). Electrolysis caused by electric fields is expected to lead torelease of platinum into the region around the tumor. Platinum is knownto exert a cytotoxic effect on cancer cells, and therefore, release ofplatinum into the tumor may advantageously increase the anti-cancereffect of the TTFields treatment.

Optionally, in any of the embodiments described above, the transducerarrays A, B and the electronics E that are implanted into the patient'shead may be designed as described below in connection with FIG. 7 . Theadvantage of this configuration is that average field intensity can bemaximized while minimizing the risk of heating by monitoring andadjusting the current to each electrode element in each transducer arrayindependently, thereby improving the efficiency of TTFields delivery.These embodiments operate by alternately switching the current on andoff for each individual electrode element that begins to overheat inorder to reduce the average current for those electrode elements,without affecting the current that passes through the remainingelectrode elements (which are not overheating).

Assume, for example, a situation in which 500 mA of current is passingthrough a transducer array that includes 10 electrode elements, and onlya single one of those electrode elements begins to overheat. Assumefurther that a 10% reduction of current through the single electrodeelement would be necessary to prevent that single electrode element fromoverheating. The embodiments described herein can cut the averagecurrent through the single electrode element by 10% by switching thecurrent through that single electrode element on and off with a 90% dutycycle, while leaving the current on full-time for all the remainingelectrode elements. Note that the switching rate must be sufficientlyfast so that the instantaneous temperature at the single electrodeelement is never too hot, in view of the thermal inertia of theelectrode elements. For example, a 90% duty cycle could be achieved byswitching the current on for 90 ms and switching the current off for 10ms. In some preferred embodiments, the period of switching the currenton and off is less than 1 s.

When this approach is used, the current through the remaining 9electrode elements can remain unchanged (i.e., 50 mA per electrodeelement), and only the current through the single electrode element isreduced to an average of 45 mA. The average net total current throughthe transducer array will then be 495 mA (i.e., 9×50+45), which meansthat significantly more current can be coupled into the person's bodywithout overheating at any of the electrode elements.

The system may even be configured to increase the current through theremaining nine electrode elements in order to compensate for thereduction in current through the single electrode element. For example,the current through the remaining nine electrode elements could beincreased to 50.5 mA per electrode element (e.g., by sending a requestto the AC voltage generator to increase the voltage by 1%). If thissolution is implemented, the average net total current through theentire transducer array would be (9 electrodes×50.5 mA+1 electrode×50.5mA×0.9 duty cycle)=499.95 mA, which is extremely close to the original500 mA of current.

If, at some subsequent time (or even at the same time), the temperatureat a second electrode element begins to overheat, a similar technique(i.e. a reduction in the duty cycle from 100% to something less than100%) may be used to prevent the second electrode element fromoverheating.

In some embodiments, this technique may be used to individuallycustomize the duty cycle at each of the electrode elements in order tomaximize the current that flows through each of those electrode elementswithout overheating. Optionally, instead of taking remedial action toreduce the duty cycle only when a given electrode element begins tooverheat, the system may be configured to proactively set the duty cycleat each of the electrode elements in a given transducer arrayindividually so as to equalize the temperature across all of theelectrode elements in the array. For example, the system could beconfigured to individually set the duty cycle at each electrode elementso as to maintain a temperature that hovers around a set temperature ateach of the electrode elements. Optionally, the system may be configuredto send a request to the AC voltage generator to increase or decreasethe voltage as required in order to achieve this result.

This approach can be used to ensure that each and every electrodeelement will carry the maximum average current possible (withoutoverheating), which will provide an increased field strength in thetumor and a corresponding improvement in the treatment.

FIG. 7 depicts an embodiment that periodically switches the current onand off for each individual electrode element that begins to overheat.The hub/AC voltage generator 30 has two outputs (OUT1 and OUT2), each ofwhich has two terminals. The hub/AC voltage generator generates an ACsignal (e.g. a 200 kHz sine wave) between the two terminals of each ofthose outputs in an alternating sequence (e.g., activating OUT1 for 1sec., then activating OUT2 for 1 sec., in an alternating sequence). Apair of conductors 51 are connected to the two terminals of OUT1, andeach of those conductors 51 goes to a respective one of the left andright transducer assemblies 31, 32. Each of these transducer assembliesincludes a plurality of electrode elements 52 (which collectivelycorrespond to the transducer arrays A, B in FIGS. 2-6 ) and electroniccomponents 56, 85 (which correspond to the electronics E in FIGS. 2-6 ).A second pair of conductors 51 are connected to the two terminals ofOUT2 and each of those conductors 51 goes to a respective one of thefront and back transducer assemblies (not shown). The construction andoperation of the front and back transducer assemblies is similar to theconstruction of the left and right transducer assemblies 31, 32 depictedin FIG. 7 .

Each of the transducer assemblies 31, 32 includes a plurality ofelectrode elements 52. In some preferred embodiments, each of theseelectrode elements 52 is a capacitively coupled electrode element.However, in this FIG. 7 embodiment, instead of wiring all of theelectrode elements 52 in parallel, an electrically controlled switch (S)56 is wired in series with each electrode element (E) 52, and all ofthese S+E combinations 56+52 are wired in parallel. Each of the switches56 is configured to switch on or off independently of other switchesbased on a state of a respective control input that arrives from thedigital output of the respective controller 85. When a given one of theswitches 56 is on (in response to a first state of the respectivecontrol input), current can flow between the electrical conductor 51 andthe respective electrode element 52. Conversely, when a given one of theswitches 56 is off (in response to a second state of the respectivecontrol input), current cannot flow between the electrical conductor 51and the respective electrode element 52.

In some preferred embodiments, each of the capacitively coupledelectrode elements 52 is disc-shaped and has a dielectric layer on oneside.

In some preferred embodiments, each of the capacitively coupledelectrode elements 52 comprises a conductive plate with a flat face, andthe dielectric layer is disposed on the flat face of the conductiveplate. In some preferred embodiments, all of the capacitively coupledelectrode elements are held in place by a support structure. In somepreferred embodiments, the electrical connection to each of theelectrode elements 52 comprises a trace on a flex circuit.

Each of the transducer assemblies 31, 32 also includes a temperaturesensor 54 (e.g., a thermistor) positioned at each of the electrodeelements 52 so that each temperature sensor 54 can sense the temperatureof a respective electrode element 52. Each of the temperature sensors 54generates a signal indicative of the temperature at (e.g., beneath) therespective electrode element 52. The signals from the temperaturesensors 54 are provided to the analog front and of the respectivecontroller 85.

In embodiments where thermistors are used as the temperature sensors 54,temperature readings may be obtained by routing a known current througheach thermistor and measuring the voltage that appears across eachthermistor. In some embodiments, thermistor-based temperaturemeasurements may be implemented using a bidirectional analog multiplexerto select each of the thermistors in turn, with a current source thatgenerates a known current (e.g., 150 μA) positioned behind themultiplexer, so that the known current will be routed into whicheverthermistor is selected by the analog multiplexer at any given instant.The known current will cause a voltage to appear across the selectedthermistor, and the temperature of the selected thermistor can bedetermined by measuring this voltage. The controller 85 runs a programthat selects each of the thermistors in turn and measures the voltagethat appears across each of the thermistors (which is indicative of thetemperature at the selected thermistor) in turn. An example of suitablehardware and procedures that may be used to obtain temperature readingsfrom each of the thermistors is described in US 2018/0050200, which isincorporated herein by reference in its entirety.

In some preferred embodiments, the controller 85 may be implementedusing a single-chip microcontroller or Programmable System on Chip(PSoC) with a built in analog front end and multiplexer. Suitable partnumbers for this purpose include the CY8C4124LQI-443. In alternativeembodiments, other microcontrollers may be used with either built-in ordiscrete analog front ends and multiplexers, as will be apparent topersons skilled in the relevant arts.

In alternative embodiments, not shown, an alternative approach (e.g.,the conventional voltage divider approach) for interfacing with thethermistors may be used in place of the constant current approachdescribed above. In other alternative embodiments, a different type oftemperature sensor may be used in place of the thermistors describedabove. Examples include thermocouples, RTDs, and integrated circuittemperature sensors such as the Analog Devices AD590 and the TexasInstruments LM135. Of course, when any of these alternative temperaturesensors is used, appropriate modifications to the circuit (which will beapparent to persons skilled in the relevant arts) will be required.

In some embodiments, the controller 85 is programmed to keep thetemperature at all of the electrode elements below a safety thresholdusing intelligence that is built into each transducer assembly 31. Thismay be accomplished, for example, by programming the controller 85 tostart out by setting its digital output so that each of the switches 56is continuously on (i.e., with a 100% duty cycle). Then, based onsignals arriving via the controller 85 analog front end, the controller85 determines whether the temperature at each of the electrode elementsexceeds an upper threshold that is below the safety threshold. When thecontroller 85 detects this condition, the controller 85 reduces the dutycycle for the corresponding switch 56 by toggling the correspondingdigital output at the desired duty cycle. This will interrupt thecurrent to the corresponding electrode element 52 at the same dutycycle, thereby reducing the average current at the specific electrodeelements 52 whose temperature exceeds that upper threshold. The level ofreduction in current is determined by the duty cycle. For example, usinga 50% duty cycle will cut the current by half; and using a 75% dutycycle will cut the current by 25%.

Notably, this procedure only interrupts the current to specific ones ofthe electrode elements 52 on the transducer assembly 31, and does notinterrupt the current to the remaining electrode elements 52 on thattransducer assembly 31. This eliminates or reduces the need to cut thecurrent that is being routed through the electrode elements when only asmall number of those electrode elements are getting hot.

A numeric example will be useful to illustrate this point. Assume, inthe FIG. 7 embodiment, that the left and right transducer assemblies 31,32 are implanted on the left and right sides of a subject's head,respectively; that all of the switches 56 in the transducer assemblies31, 32 are in the ON state with a 100% duty cycle; and that the hub/ACvoltage generator 30 is initially outputting 500 mA of current into theconductors 51. An AC voltage will appear between the electrode elements52 of the left transducer assembly 31 and the electrode elements 52 ofthe right transducer assembly 32, and the 500 mA AC current will becapacitively coupled through the electrode elements 52 through thesubject's head. The controller 85 in each of the transducer assemblies31, 32 monitors the temperature at each of the electrode elements 52 inthat transducer assembly by inputting signals from each of thetemperature sensors 54 via the analog front end of the controller 85.Now assume that a given one of the electrode elements 52 in thetransducer assembly 31 begins to overheat. This condition will bereported to the controller 85 in the transducer assembly 31 via a signalfrom the corresponding temperature sensor 54. When the controller 85recognizes that the given electrode element 52 is overheating, thecontroller 85 will toggle the control signal that goes to thecorresponding switch 56 at the desired duty cycle in order toperiodically interrupt the current to the given electrode element 52 andmaintain a lower average current.

Note that if the duty cycle at only one of the remaining electrodeelements 52 is being reduced, it may be possible to maintain theoriginal 500 mA current (and enjoy the advantages that arise from usingthe full current). However, if the duty cycle at a large enough numberof the electrode elements 52 is being reduced, the original 500 mAcurrent may have to be dropped. To accomplish this, the controller 85can send a request to the hub/AC voltage generator 30 via the UART inthe controller 85. When the hub/AC voltage generator 30 receives thisrequest, the hub/AC voltage generator 30 will reduce the output currentat its corresponding output OUT1.

Optionally, the duty cycle that is selected by the controller 85 may becontrolled based on the speed at which the given electrode element 52heats up after current is applied to the given electrode element 52 (asmeasured via the temperature sensors 54 and the analog front end of thecontroller 85). More specifically, if the controller 85 recognizes thata given electrode element 52 is heating up twice as fast as expected,the controller 85 can select a duty cycle of 50% for that electrodeelement. Similarly, if the controller 85 recognizes that a givenelectrode element 52 is heating up 10% faster than expected, thecontroller 85 can select a duty cycle of 90% for that electrode element.

In other embodiments, instead of deterministically cutting the averagecurrent by reducing the duty cycle, the controller 85 can reduce theaverage current at a given electrode element 52 based on real-timetemperature measurements by turning off the current to the givenelectrode element 52 and waiting until temperature measured using thetemperature sensors 54 drops below a second temperature threshold. Oncethe temperature drops below this second temperature threshold, thecontroller 85 can restore the current to the given electrode element 52.This may be accomplished, for example, by controlling the state of thecontrol input to the switch 56 that was previously turned off so thatthe switch 56 reverts to the ON state, which will allow current to flowbetween the electrical conductor and the respective electrode element52. In these embodiments, the current to a given electrode element 52may be repeatedly switched off and on based on real-time temperaturemeasurements in order to keep the temperature at the given electrodeelement 52 below the safety threshold.

In the FIG. 7 embodiment, each of the transducer assemblies 31, 32 isconnected to the hub/AC voltage generator 30 via a respective cable.Notably only 4 conductors are required in each of the cables that runbetween the transducer assembly and the hub/AC voltage generator 30(i.e., Vcc, data, and ground for implementing serial data communication,plus one additional conductor 51 for the AC current TTFields signal).

Note that in FIG. 7 , each transducer assembly 31, 32 includes nineelectrode elements 52, nine switches 56, and nine temperature sensors54. But in alternative embodiments, each transducer assembly 31, 32 caninclude a different number (e.g., between 8 and 25) of electrodeelements 52 and a corresponding number of switches and temperaturesensors.

In these embodiments, the decision to adjust the duty cycle or turn offone or more of the switches 56 in a given transducer assembly 31, 32 inorder to reduce the average current to one or more of the electrodeelements 52 is made locally in each transducer assembly 31, 32 by thecontroller 85 within that transducer assembly 31, 32. But in alternativeembodiments, the decision to adjust the duty cycle or turn off one ormore of the switches 56 may be made by the hub/AC voltage generator 30(or another remote device). In these embodiments, the controller 85 ineach of the transducer assemblies 31, 32 obtains the temperaturereadings from each of the temperature sensors 54 in the respectivetransducer assembly and transmits those temperature readings to thehub/AC voltage generator 30 via the UART of the controller 85. Thehub/AC voltage generator 30 decides which, if any, of the switchesrequire a duty cycle adjustment or should be turned off based on thetemperature readings that it received, and transmits a correspondingcommand to the corresponding controller 85 in the correspondingtransducer assembly 31, 32. When the controller 85 receives this commandfrom the hub/AC voltage generator 30, the controller 85 responds bysetting its digital output to a state that will switch off thecorresponding switch 56 at the appropriate times, in order to carry outthe command that was issued by the hub/AC voltage generator 30. In theseembodiments, the hub/AC voltage generator 30 can also be programmed toreduce its output current if a reduction in current is necessary to keepthe temperature at each of the electrode elements 52 below the safetythreshold.

In these embodiments, the controller 85 may be programmed to operate asa slave to a master controller located in the hub/AC voltage generator30. In these embodiments, the controller 85 starts out in a quiescentstate, where all it does is monitor incoming commands from the mastercontroller that arrive via the UART. Examples of commands that canarrive from the master controller include a “collect temperature data”command, a “send temperature data” command, and a “set switches”command. When the controller 85 recognizes that a “collect temperaturedata” command has arrived, the controller 85 will obtain temperaturereadings from each of the temperature sensors 54 and store the result ina buffer. When the controller 85 recognizes that a “send temperaturedata” command has arrived, the controller 85 will execute a procedurethat transmits the previously collected temperature readings from thebuffer to the hub/AC voltage generator 30 via the UART 86. And when thecontroller 85 recognizes that a “set switches” command has arrived, thecontroller 85 will execute a procedure to output appropriate voltages onits digital output in order to set each of the switches 56 to a desiredstate (i.e., either ON, OFF, or switching between on and off at acommanded duty cycle) based on data that arrives from the hub/AC voltagegenerator 30.

In the embodiments described above, a single controller 85 is used ineach of the transducer assemblies 31, 32 to control the switches 56 inthat assembly and also to obtain temperature measurements from each ofthe temperature sensors 54 in that assembly. In alternative embodiments,instead of using a single controller 85 to control the switches 56 andto obtain the temperature measurements, those two tasks may be dividedbetween two controllers, one of which is only used to control theswitches 56, and the other of which is used to obtain the temperaturemeasurements from each of the temperature sensors 54 (e.g., using any ofthe approaches described above). In these embodiments, these twocontrollers may communicate directly with each other, and/or the hub/ACvoltage generator 30.

In other alternative embodiments (not shown), temperature measurementdoes not rely on a local controller that is positioned in the vicinityof the electrode elements 52. Instead, wires run from each of thetemperature sensors 54 back to the hub/AC voltage generator 30, and thehub/AC voltage generator uses signals that arrive via these wires todetermine the temperature at each of the temperature sensors 54.

FIG. 8 is a schematic diagram of a circuit that is suitable forimplementing the switches 56, 56′ in the FIG. 7 embodiment describedabove. The circuit includes two field effect transistors 66, 67 wired inseries, which is a configuration that can pass current in eitherdirection. One example of a suitable FET for this circuit is theBSC320N20NSE. (Note that the diodes depicted in FIG. 8 are inherentlyincluded within the FETs 66, 67 themselves.) The series combination ofthe two FETs 66, 67 will either conduct or block the flow ofelectricity, depending on the state of the control input that arrivesfrom one of the digital outputs of the controller 85 described above.When the series combination is conducting, current can flow between theshared conductor 51 and the respective electrode element 52, 52′. On theother hand, when the series combination of FETs 66, 67 is notconducting, current will not flow between the shared conductor 51 andthe respective electrode element 52, 52′.

Optionally, a current sensing circuit 60 may be positioned in serieswith the switch 56, 56′. The current sensing circuit 60 may beimplemented using any of a variety of conventional approaches that willbe apparent to persons skilled in the relevant arts. When the currentsensing circuit 60 is included, it generates an output that isrepresentative of the current, and this output is reported back to thecontroller 85 (shown in FIG. 7 ). The controller 85 can then use thisinformation to determine whether the measured current is as expected andtake appropriate action if necessary. For example, if an overcurrentcondition is detected, the controller 85 can turn off the correspondingswitch. Of course, in those embodiments where the current sensingcircuit 60 is omitted, it should be replaced with the wire (or otherconductor) so that the current can flow between the shared conductor 51and the top leg of the upper FET 60.

In the illustrated embodiment, the current sensing circuit 60 ispositioned between the shared conductor 51 and the top leg of the upperFET 60. But in alternative embodiments, the current sensing circuit maybe positioned between the bottom leg of the lower FET 67 and therespective electrode element 52, 52′. And in other alternativeembodiments (not shown), the current sensing circuit may be integratedwithin the circuitry of the switch itself.

While the present invention has been disclosed with reference to certainembodiments, numerous modifications, alterations, and changes to thedescribed embodiments are possible without departing from the sphere andscope of the present invention, as defined in the appended claims.Accordingly, it is intended that the present invention not be limited tothe described embodiments, but that it has the full scope defined by thelanguage of the following claims, and equivalents thereof.

1. An apparatus for delivering tumor treating fields, the apparatuscomprising: a plurality of sets of electrode elements, wherein each ofthe sets of electrode elements is configured for implantation within aperson's body; a plurality of temperature sensors configured forimplantation within the person's body and positioned to measure atemperature at each of the sets of electrode elements; and at least onecircuit configured for implantation within the person's body, whereinthe at least one circuit is configured and positioned to reduce a numberof conductors that are required to obtain temperature measurements fromthe plurality of temperature sensors and to forward the obtainedtemperature measurements to an output.
 2. The apparatus of claim 1,wherein each of the sets of electrode elements comprises a plurality ofcapacitively coupled electrode elements.
 3. The apparatus of claim 1,wherein each of the temperature sensors comprises a thermistor.
 4. Theapparatus of claim 1, wherein the plurality of sets of electrodeelements, the plurality of temperature sensors, and the at least onecircuit are all implanted in the person's body.
 5. The apparatus ofclaim 1, wherein each of one or more electrode elements in each of thesets of electrode elements is associated with a respective one of thetemperature sensors.
 6. The apparatus of claim 1, wherein each of theelectrode elements is associated with a respective one of thetemperature sensors.
 7. The apparatus of claim 6, wherein the at leastone circuit is configured to control a current that is applied to eachindividual electrode element based on signals from the plurality oftemperature sensors so that the electrode elements do not overheat. 8.The apparatus of claim 1, wherein the at least one circuit comprises aUART configured to implement serial data communication.
 9. An apparatusfor delivering tumor treating fields, the apparatus comprising: aplurality of sets of electrode elements, wherein each of the sets ofelectrode elements is configured for implantation within a person'sbody; and a plurality of temperature sensors configured for implantationwithin the person's body and positioned to measure a temperature at eachof the sets of electrode elements.
 10. The apparatus of claim 9, whereineach of the sets of electrode elements comprises a plurality ofcapacitively coupled electrode elements.
 11. The apparatus of claim 9,wherein each of the temperature sensors comprises a thermistor.
 12. Theapparatus of claim 9, wherein the plurality of sets of electrodeelements and the plurality of temperature sensors are all implanted inthe person's body.
 13. The apparatus of claim 9, wherein each of one ormore electrode elements in each of the sets of electrode elements isassociated with a respective one of the temperature sensors.
 14. Theapparatus of claim 9, wherein each of the electrode elements isassociated with a respective one of the temperature sensors.
 15. Theapparatus of claim 9, further comprising a plurality of switches and acontroller, wherein the controller is programmed to (a) determine when atemperature at a given electrode element exceeds a threshold value basedon a signal from a respective one of the temperature sensors and (b)reduce a duty cycle at a corresponding one of the switches in order toreduce an average current at the given electrode element.
 16. Theapparatus of claim 9, further comprising a plurality of switches and acontroller, wherein the controller is programmed to (a) determine howfast a given electrode element heats up based on a signal from arespective one of the temperature sensors and (b) select a duty cyclefor a corresponding one of the switches based on the determined heatingspeed.
 17. The apparatus of claim 9, further comprising a plurality ofswitches and a controller, wherein the controller is programmed to (a)determine when a temperature at a given electrode element exceeds athreshold value based on a signal from a respective one of thetemperature sensors, (b) subsequently switch off current to the givenelectrode element by sending a first control signal to a correspondingone of the switches, (c) subsequently determine when a temperature atthe given electrode element drops below a second temperature threshold,and (d) subsequently restore the current to the given electrode elementby sending a second control signal to the corresponding one of theswitches.